Wide presence of radioactive material for therapeutic, energy, or weapons underscores the need for medical preparedness for effective treatment of either accidental or intentional exposure. High energy radiation exposure (e.g. gamma radiation or X-rays) from cancer radiotherapy, or from acute radiation exposure, such as from the broad dissemination of radioactive materials in water or air (e.g. a “dirty bomb”, a nuclear power catastrophe, or a nuclear explosion) can penetrate the body and cause harmful effects such as cell death and tissue damage. Cosmic rays and solar flares are another form of high energy radiation experienced during solar flares, at high altitudes and in outer space, which can lead to similar tissue injury. When the gastrointestinal (GI) tract is affected, radiation can lead to oral mucositis (head and neck radiation), esophagitis typically thoracic radiation), and radiation enteritis and colitis (due to abdominal and pelvic radiation), and more broadly, gastrointestinal acute radiation syndrome (GI-ARS). Currently there is no medical therapy or countermeasure approved to prevent, treat or mitigate radiation toxicity post-exposure, other than secondary and supportive care.
One of the acute physiological effects of irradiation is acute radiation syndrome (ARS), which first manifests in the gastrointestinal tract (GI-ARS). The acute phase occurs within days of radiation exposure, resulting from loss of intestinal clonogenic cells that lead to loss of epithelial crypts and ulceration. Symptoms and complications include weight loss, diarrhea, dehydration, susceptibility to infection, and translocation of bacteria and toxins as the intestinal mucosal barrier is compromised. Bacterial translocation from the intestine to blood and endotoxemia can lead to septic shock and death.
Radiation injury can also lead to delayed effects of acute radiation exposure (GI-DEARE). Similar to ARS, delayed effects of radiation exposure also have adverse health effects. This is evident from the Japanese survivors of high-dose radiation exposure, and also from radiation oncotherapy. Patients receiving radiation cancer treatment can frequently develop both acute and delayed GI enteropathies months and years post-therapy. In the delayed effects, there is a high incidence of GI symptoms of diarrhea, constipation, obstruction, fistulation, severe inflammatory response syndrome and sepsis, occurring in 50% of the patients with pelvic tumors receiving therapy.
Characterization of GI-ARS links to other syndromes, such as the hematopoetic system (H-ARS). All radiation doses that induce GI-ARS will have a major impact on bone marrow. This will affect the severity of GI inflammation and infection due to bacterial translocation through the impaired gut epithelium. The major organ sequelae to high-dose radiation involve other organ damage as well. Lung injury, for example, results from the DEARE. Cytokines, bacterial toxins and other inflammatory mediators play an important role in the illness. Decreasing inflammation may offer a promising therapy. For example, a number of studies correlated reduction of inflammation with anti-cancer efficacy.
Each of these conditions is typically associated with high morbidity and mortality. Therefore, it is imperative to come up with treatments for the prevention (termed a radioprotector) and mitigation (termed a mitigator) of both the acute and delayed adverse effects of radiation exposure.